Giuliani Laura, Ronci Corrado, Bonifacio Daniela, Di Bonito Luigi, Favalli Cartesio, Perno Carlo Federico, Syrjänen Kari, Ciotti Marco
Laboratory of Molecular Virology, University Hospital Tor Vergata, Rome, Italy.
Anticancer Res. 2008 Mar-Apr;28(2B):1405-10.
As a part of our search for oncogenic viruses as potential etiological agents in human malignancies, our studies on human papillomaviruses (HPV) were extended to analysis of the 3 polyomaviruses (SV40, BKV and JCV) in colorectal carcinomas.
Archival tumour samples from 71 patients with colorectal cancer were analyzed for the sequences of SV40, BKV, JCV and HPV using PCR-based techniques. HPV genotypes were determined using sequencing and reverse blot hybridization (InnoLipa).
Amplification of BKV and JCV with the primer pair PEP-1 and PEP-2 and subsequent restriction digestion of the amplified products with BamH I disclosed BKV in 6/66 (9%) of the samples, whereas none contained JCV. SV40 was amplified in 10/66 (15.1%) samples and confirmed by sequencing analysis. In pair-wise analysis for co-infections, the samples were significantly different in their BKV-JCV and JCV-SV40 status, in contrast to their BKV-SV40 co-infection status. HPV DNA was detected in 22/66 (33.3%) of the samples analysed with either the MY09/11 or SPF primer mix. Of these 22 HPV infections, 7 were single-type infections and 15 contained multiple HPV types. HPV detection or type distribution showed no relationship to the gender of the patients or histological grade of the tumour. HPV status was not significantly related to detection of BKV, JCV or SV40. Similarly, in pair-wise analysis for co-infections, the samples were significantly different in their status of HPV-BKV (p=0.0006), HPV-JCV (p=0.0001), and HPV-SV40 (p=0.019), implicating that HPV and the 3 polyomaviruses are rarely detected concomitantly in the same samples.
Taking the known molecular mechanisms of action of these individual viruses, there is a chance that these viruses could alter the mechanisms of cell cycle control and inhibit apoptosis, thus potentially causing chromosomal instability and promoting colorectal oncogenesis.
作为我们寻找致癌病毒作为人类恶性肿瘤潜在病因的一部分，我们对人乳头瘤病毒（HPV）的研究扩展到了对结直肠癌中3种多瘤病毒（SV40、BKV和JCV）的分析。
使用基于PCR的技术对71例结直肠癌患者的存档肿瘤样本进行SV40、BKV、JCV和HPV序列分析。使用测序和反向斑点杂交（InnoLipa）确定HPV基因型。
用引物对PEP-1和PEP-2扩增BKV和JCV，并随后用BamH I对扩增产物进行限制性消化，结果显示6/66（9%）的样本中存在BKV，而无一例样本含有JCV。10/66（15.1%）的样本中扩增出SV40，并经测序分析证实。在共感染的成对分析中，样本在BKV-JCV和JCV-SV40状态方面存在显著差异，而在BKV-SV40共感染状态方面则不然。在用MY09/11或SPF引物混合物分析的样本中，22/66（33.3%）检测到HPV DNA。在这22例HPV感染中，7例为单型感染，15例含有多种HPV类型。HPV检测或类型分布与患者性别或肿瘤组织学分级无关。HPV状态与BKV、JCV或SV40的检测无显著相关性。同样，在共感染的成对分析中，样本在HPV-BKV（p=0.0006）、HPV-JCV（p=0.0001）和HPV-SV40（p=0.019）状态方面存在显著差异，这表明HPV和这3种多瘤病毒很少在同一样本中同时被检测到。
鉴于这些病毒各自已知的分子作用机制，这些病毒有可能改变细胞周期控制机制并抑制细胞凋亡，从而潜在地导致染色体不稳定并促进结直肠癌的发生。
